Micromechanical Device for Intracochlear Drug Delivery GRANTING NIH INSTITUTE/CENTER: National Institute on Deafness and Other Communication Disorders (NIDCD) GRANT NUMBER: DC006848 ABSTRACT Recent developments in cochlear physiology and molecular biology have paved the way for new and innovative ways of treating and preventing sensorineural hearing loss. These advances will ultimately benefit millions of individuals. However, for this to occur, it will be necessary to develop a safe and reliable mechanism for delivering bioactive compounds directly to the inner ear. The goal of this collaborative research effort is to design and develop a versatile long-term drug delivery system for the treatment of inner ear disorders. Working together, biomedical engineers from Draper Laboratory with experience and expertise in the development of drug delivery microsystems, and clinicians and scientists from the Massachusetts Eye and Ear Infirmary with expertise in inner ear physiology, pharmacology and otologic surgery will engineer, evaluate and perfect a drug delivery system for the treatment of inner ear disorders. This device will have broad application and the potential for revolutionizing the treatment of hearing loss. The design concept includes an implanted device that fits within the mastoid cavity of humans. The device contains an externally-programmable, implanted pump to recirculate perilymph, an intracochlear catheter inserted into the scala tympani, a reservoir and mixing chamber for delivery of concentrated bioactive compounds, and sensors for detecting and transmitting flow and pressure information. The ultra-miniaturized device is a complete, long-term (two year and greater) delivery system, containing therapeutic compound, dispensing mechanism, control electronics, and power supply. Its development takes advantage of recent developments in microfluidics and MEMS (MicroElectroMechanical Systems) technologies. In the previous project period, we developed and tested a microfluidics-based, wearable drug delivery device and demonstrated it in a guinea pig model using a novel reciprocating delivery paradigm. The aims of the renewal proposal are to (1) Develop precision control of drug delivery throughout the cochlea by establishing and demonstrating a computational model that incorporates the fluid dynamic aspects of our drug delivery into previous models of solute kinetics and translates to human clinical applications;(2) Design and build an implantable microfluidic module including a micropump, flow sensor, fluid distribution network and drug reservoir;and (3) Design and build an electronic control and power module and integrate with the microfluidic module from Aim 2, producing a fully implantable prototype for human clinical use with the first application targeted at steroid-responsive autoimmune inner ear disease. PUBLIC HEALTH RELEVANCE: The ultimate goal of this project is to develop a device capable of delivering drugs directly to the inner ear of patients suffering from hearing loss and other diseases related to hearing and balance. The device will be implanted and will be programmable to deliver drugs locally to the inner ear, thereby avoiding side effects and problems with drugs reaching their target typically experienced by patients using oral or injected medications. The near-term application of the technology will be to develop an implantable drug delivery system for steroid- responsive autoimmune inner ear disease, avoiding the systemic side effects of steroids while treating the disease and preserving patients'hearing.